Danazol suppresses the production of interleukin-1 beta and tumor necrosis factor by human monocytes.
The effects of estradiol (E2), progesterone (P), and danazol on the production of interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF) by OK-432 (a streptococcal preparation)-stimulated monocytes were examined. E2 and P at physiologic concentrations enhanced IL-1 beta and TNF production by monocytes from donors with lower control levels (without steroids added) of IL-1 beta and TNF. However, E2 and P at physiologic concentrations did not affect IL-1 beta and TNF production by monocytes from donors with higher control levels of IL-1 beta and TNF. Danazol inhibited IL-1 beta and TNF production by monocytes in a dose-dependent manner from not only donors with lower control levels of IL-1 beta and TNF but also donors with higher control levels of IL-1 beta and TNF. Danazol at a concentration of 10(-6) M significantly suppressed IL-1 beta and TNF production in the presence of E2 and/or P at concentrations giving peak responses of IL-1 beta production. These findings suggest possible new mechanisms of action for danazol in the treatment of endometriosis and infertility associated with immune abnormalities.
Mori
H
H
Department of Obstetrics and Gynecology, Gifu University School of Medicine, Japan.
Nakagawa
M
M
Itoh
N
N
Wada
K
K
Tamaya
T
T
D000328:Adult; D003613:Danazol / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010844:Picibanil / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D010844:Picibanil; D011374:Progesterone; D004958:Estradiol; D003613:Danazol